This research has two objectives: The development of in vitro predictive techniques to permit estimation of the response of solid tumors to chemotherapeutic agents and the utilization of such results for the design of multiple drug protocols for the treatment of human malignancies. Particular emphasis is placed on attempts to eliminate non-cycling cells. For this purpose in vitro chemotherapy is carried out on plateau-phase cultures and on exponentially growing cultures to determine the relative drug cytotoxicity. The ability of such cells to repair potentially lethal lesions is examined and attempts are made to interfere with this repair, utilizing modalities such as X-irradiation, elevated temperature or other chemotherapeutic agents. Experiments are also carried out utilizing a transplantable murine mammary tumor adapted to in vitro growth so that experiments can be carried out in vivo while assay to measure clonogenicity of tumor cells is carried out in vitro. Promising drugs found utilizing the in vitro screen are then tested in the mouse system. Repair effects are examined by cell survival of tumors excised at different times after drug injection. Multiple drug protocols designed to maximally eliminate the non-cycling tumor cells are tested as "remission induction" regimens. The interaction of hyperthermia and therapeutic agents are investigated in vitro, again with concomitant tests in vivo of promising combinations. BIBLIOGRAPHIC REFERENCES: G. M. Hahn, J. Braun, and I. Har-Kedar, Thermochemotherapy: Synergism between hyperthermia (42 degrees C-43 degrees C) and adriamycin ( or bleomycin) in mammalian cell inactivation. Proc. Natl. Acad. Sci. USA. 72, 937-940 (1975). K. Kase and G. M. Hahn, Differential heart response of normal and transformed human cells in tissue culture. Nature 255, 230-288 (1975).